Our previous studies suggested that the relative resistance of young gerbils may be attributed to neuronal function On the other hand, the ischemic induction of heat shock protein HSP72 has been suggested to play a protective role against neuronal injury. To elucidate further, the mechanisms responsible for the observed are dependent upon susceptibility to brain ischemia, we investigated the effect of ischemia on HSP72 expression at both transcriptional and translational levels in the hippocampus of young and adult gerbils. The HSP72 RNA expression was observed in all hippocampal areas within 3 hr of reflow, reaching a maximum by 8 hr of reflow in both young and adult gerbils. However, a much stronger in situ hybridization was observed at 1 hr of reperfusion in the hippocampus of young than that seen in adult animals. A progressive decrease in HSP72 mRNA expression was seen in various areas of the hippocampus except CA1. At 48 hr, the persisting expression of mRNA in CA1 was more marked in young than adult gerbils. The appearance of HSP72 protein was detected at a later time than that observed for mRNA. The most striking difference was seen in CA1 neurons which showed a more marked accumulation of HSP72 protein in young than that observed in adult animals. These studies strongly suggest that the immature neurons possess an endogenous tolerance to ischemia that may be related to higher transcriptional activity.